No increased risk of hepatic enzyme abnormalities with non‑peptidic thrombopoietin receptor agonists in immune thrombocytopenia: A meta‑analysis of randomized controlled trials

Non-peptidic thrombopoietin receptor agonists (TPO-RAs), including eltrombopag, avatrombopag and hetrombopag, are used as second-line therapies for immune thrombocytopenia (ITP). However, concerns regarding their hepatic safety persist. The present study conducted a meta-analysis by searching PubMed, Web of Science and the Chinese Medical Association Journal Database for randomized controlled trials evaluating non-peptidic TPO-RAs in ITP that reported hepatic enzyme outcomes, specifically alanine aminotransferase and/or aspartate aminotransferase. The present meta-analysis therefore assessed data from 13 randomized controlled trials involving 1,480 patients (1,034 in the intervention arm and 446 in the control arm) to evaluate the risk of hepatic enzyme abnormalities associated with these aforementioned agents. The results revealed that non-peptidic TPO-RAs did not significantly increase the incidence of hepatic enzyme elevation events in the intervention group compared with that in the control group [odds ratio (OR)=1.30; 95% CI, 0.82-2.07; P=0.27]. The risk of hepatic enzyme elevation events in patients receiving TPO-RAs remained non-significant when analyses were restricted to studies with a treatment duration of ≥6 weeks (OR=1.28; 95% CI: 0.78-2.08; P=0.33), to studies that exclusively enrolled adults (OR=1.24; 95% CI, 0.77-1.99; P=0.37, and to studies reporting severe transaminase elevations defined as ≥3 times the upper limit of that considered normal (OR=1.66; 95% CI, 0.59-4.65; P=0.34). Subgroup analyses also showed no significant increase in hepatic enzyme elevation events with eltrombopag (OR=1.68; 95% CI, 0.93-3.04; P=0.09), avatrombopag (OR=0.88; 95% CI, 0.09-8.46; P=0.91) or hetrombopag (OR=1.04; 95% CI, 0.30-3.65; P=0.95). These findings suggest that non-peptidic TPO-RAs did not significantly increase the incidence of hepatic enzyme elevation events in patients with ITP compared with that in controls and support their continued clinical use with appropriate liver function monitoring. The present meta-analysis was registered in the International Prospective Register of Systematic Reviews (registration no. CRD420251084782).